Effect of socioeconomic status on the physical and mental health of the elderly: the mediating effect of social participation.
Previous studies have demonstrated the effect of socioeconomic status on the health status of the elderly. Nevertheless, the specific dimensions of the effect and the mechanism await further investigation. In this study, socioeconomic status was divided into three dimensions and we used social participation as the mediation variable to investigate the specific path of effect. Using the 2018 Waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, a total of 10,197 effective samples of the elderly over 65 years old were screened out. Socioeconomic status included income, education level, and main occupation before retirement. The physical health and mental health of the elderly was measured by the Instrumental Activities of Daily Living Scale and the Minimum Mental State Examination, respectively. The social participation of the elderly was the mediation variable, including group exercise, organized social activities and interacting with friends. Omnibus mediation effect analysis was adopted to examine the mediation effect and mediation analysis was completed using the SPSS PROCESS program. First, the results showed that when the income gap between the elderly reached a certain level, there was a significant difference in health status. Significant differences existed in health status amongst with different education levels. There was no sufficient evidence to show that occupation has a significant effect on the physical health. But when the dependent variable was mental health, the effect was significant. Second, group exercise mediated 64.11% (aib = 0.24, 95% CI [0.17,0.3]) and up to 20.44% (aib = 0.12, 95% CI [0.07,0.17]) of the disparity in physical and mental health due to income gap, respectively. And it could mediate the effect up to 56.30% (aib = 0.62, 95% CI [0.52,0.73]) and 17.87% (aib = 0.50, 95% CI [0.4,0.61]) of education on physical and mental health status, respectively. The proportion of relative mediation effect of occupation was up to 28.74% (aib = 0.19, 95% CI [0.13,0.25]) on mental health. Interacting with friends mediated only on the path that the education affected the health status of the elderly. The proportion was up to 33.72% (aib = 0.29, 95% CI [0.16,0.44]). The relative mediation effect of organized social activities on the health gap caused by income or education level gap was significant at some levels. The proportion was up to 21.20% (aib = 0.33, 95% CI [0.26,0.4]). The SES of the elderly including relatively large income gap, different education levels and occupational categories could indeed have a significant effect on health status of the elderly, and the reason why this effect existed could be partly explained by the mediation effect of social participation. Policymakers should pay more attention to the social participation of the elderly.


Imagine you are dying: would you be interested in having a hospice palliative care volunteer?
A community sample of 100 adults was asked to imagine that they had been recently diagnosed with a life-threatening illness. After reading about the services provided by hospice palliative care volunteers, participants were asked whether they would choose to have a volunteer help them and to give a reason for their answer. Eighty-nine of the 100 participants indicated that they would use the help of a volunteer. The most commonly given reasons for utilizing a volunteer included for the general support they provide, help with practical things, and lack of family nearby; reasons given for declining the services of a volunteer included "I'm a private person'' and "I don't need any help.'' Sixty-five participants knew that such a volunteer program was available. Of the 35 participants who did not, 31 (89%) expected their family doctor to tell them about it. The implications of these findings for volunteer program coordinators are discussed.


Controlled self-assembly by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes.
The complexation-induced critical aggregation concentrations of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes (n=4, 5) were systemically measured by fluorescence spectroscopy. In all cases, the complexation-induced critical aggregation concentration decreases by about 3 times upon addition of p-sulfonatocalix[n]arenes. However, the optimal molar ratios for the aggregation of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes are distinctly different: For mono-p-sulfonatocalix[n]arenes, the optimum mixing ratio for the aggregation of 1-pyrenemethylaminium is 1:4 mono-p-sulfonatocalix[n]arenes/1-pyrenemethylaminium, whereas only 2.5 molecules of 1-pyrenemethylaminium can be bound by one cavity of bis-p-sulfonatocalix[n]arenes. The intermolecular complexation of mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes with 1-pyrenemethylaminium led to the formation of two distinctly different nanoarchitectures, which were shown to be nanoscale vesicle and rod aggregates, respectively, by using dynamic laser scattering, TEM, and SEM. This behavior is also different from the fiber-like aggregates with lengths of several micrometers that were formed by 1-pyrenemethylaminium itself above its critical aggregation concentration. Furthermore, the obtained nanoaggregates exhibit benign water solubility, self-labeled fluorescence, and, more importantly, temperature responsiveness.


Chenopodium as a prehistoric domesticate in eastern north america: evidence from russell cave, alabama.
Approximately 50,000 carbonized fruits of the species Chenopodium berlandieri recovered from Russell Cave, Alabama, and dating to 1975 +/- 55 before the present, exhibit a set of interrelated morphological characteristics reflecting domestication (thin testa, truncate margin, rectanguloid fruit cross section, ligulate cotyledons, and increased internal fruit volume). These morphological characteristics establish the presence of a domestic variety of Chenopodium in the eastern United States by 2000 years ago.


Anti-GBM disease and renal vein thrombosis.
A 23-year-old female who presented with advanced renal failure was subsequently diagnosed with renal vein thrombosis and antiglomerular basement membrane (GBM) antibody disease. A previous case of renal vein thrombosis has been reported in association with anti-GBM disease, but to our knowledge, this is the first reported case in which the presentation of anti-GBM disease and renal vein thrombosis was concurrent. Further study is essential to understand if the association of anti-GBM disease and renal vein thrombosis as seen in our case was pure coincidence or is in fact occurs more frequently. It may be that the dual diagnosis is not made as establishing one sufficient diagnosis for renal failure may halt further investigations for additional diagnoses.


Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients.
Deep Vein Thrombosis (DVT) is a common complication in trauma patients. Venous duplex surveillance is used widely for the diagnosis of DVT, however, there is controversy concerning its appropriate use. The Wells criterion is a clinically validated scoring system in an outpatient setting, but its use in trauma patients has not been studied. This study evaluated the application of the Wells scoring system in trauma population. Wells scores were calculated retrospectively for all patients who were admitted to the trauma service and underwent Venous Duplex Scanning (VDS) at the author's institution between 2012 and 2013. Correlation of Wells score with DVT and its efficacy in risk stratifying the patients after trauma was analyzed using linear correlation and receiver operating characteristic (ROC) curve. Sensitivity and specificity of Wells score in ruling out or ruling in DVT were calculated in various risk groups. Of 298 patients evaluated, 18 (6 %) patients were positive for DVT. A linear correlation was present between Wells score and DVT with R (2) = 0.88 (p = 0.0016). Median Wells score of patients without DVT was 1 (1-3) compared to a median score of 2 (1-5) in those with DVT (p < 0.0001). In low risk patients (scores <1), Wells scoring was able to rule out the possibility of DVT with a sensitivity of 100 % and NPV of 100 %, while in moderate-high risk patients (scores ≥2), it was able to predict DVT with a specificity of 90 %. Area under ROC curve was 0.859 (p < 0.0001) demonstrating the accuracy of Wells scoring system for DVT risk stratification in post trauma patients. A Wells score of <1 can reliably rule out the possibility of DVT in the trauma patients. Risk of developing DVT correlates linearly with Wells score, establishing it as a valid pretest tool for risk stratification.


M1 receptor agonist activity is not a requirement for muscarinic antinociception.
The analgesic effects of a series of muscarinic agonists were investigated by use of the mouse acetic acid writhing, grid-shock, hot-plate and tail-flick tests. The compounds tested were oxotremorine, pilocarpine, arecoline, aceclidine, RS86 and four 3-3(substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahy-dro-1 -methyl pyridines (substituted TZTP), these being propoxy-TZTP, 3-Cl-propylthio-TZTP, xanomeline (hexyloxy-TZTP) and hexylthio-TZTP. These agonists were also assayed for their ability to displace [3H]oxotremorine-M and [3H]pirenz-epine binding and for their functional selectivity at pharmaco-logic M1, M2 and M3 receptors. These compounds all produced dose-dependent antinociceptive effects in all of the mouse analgesia tests. The effects of oxotremorine in the writhing test were fully antagonized by the muscarinic antagonist scopolamine (0.1 mg/kg), but only partially antagonized by methsco-polamine (10 mg/kg) and unaffected by the opioid antagonist naltrexone. 3-Cl-propylthio-TZTP and propoxy-TZTP had virtually no effect at the M1 receptor subtype as measured by the human m1 clone expressed in baby hamster kidney cells or the rabbit vas deferens assay. These compounds, however, were more potent in the analgesia tests than the selective M1 agonists xanomeline and hexylthio-TZTP. These data suggest that muscarinic analgesia is mediated by central muscarinic receptors. However, activity at the M1 receptor subtype is not a requirement for antinociceptive activity.


Modeling DNA sequence-based cis-regulatory gene networks.
Gene network analysis requires computationally based models which represent the functional architecture of regulatory interactions, and which provide directly testable predictions. The type of model that is useful is constrained by the particular features of developmentally active cis-regulatory systems. These systems function by processing diverse regulatory inputs, generating novel regulatory outputs. A computational model which explicitly accommodates this basic concept was developed earlier for the cis-regulatory system of the endo16 gene of the sea urchin. This model represents the genetically mandated logic functions that the system executes, but also shows how time-varying kinetic inputs are processed in different circumstances into particular kinetic outputs. The same basic design features can be utilized to construct models that connect the large number of cis-regulatory elements constituting developmental gene networks. The ultimate aim of the network models discussed here is to represent the regulatory relationships among the genomic control systems of the genes in the network, and to state their functional meaning. The target site sequences of the cis-regulatory elements of these genes constitute the physical basis of the network architecture. Useful models for developmental regulatory networks must represent the genetic logic by which the system operates, but must also be capable of explaining the real time dynamics of cis-regulatory response as kinetic input and output data become available. Most importantly, however, such models must display in a direct and transparent manner fundamental network design features such as intra- and intercellular feedback circuitry; the sources of parallel inputs into each cis-regulatory element; gene battery organization; and use of repressive spatial inputs in specification and boundary formation. Successful network models lead to direct tests of key architectural features by targeted cis-regulatory analysis.


Associations of serum amino acids related to urea cycle with risk of chronic kidney disease in Chinese with type 2 diabetes.
Serum levels of amino acids related to urea cycle are associated with risk of type 2 diabetes mellitus (T2DM). Our study aimed to explore whether serum levels of amino acids related to urea cycle, i.e., arginine, citrulline, and ornithine, are also associated with increased risk of chronic kidney disease (CKD) in T2DM. We extracted medical records of 1032 consecutive patients with T2DM from the Electronic Administrative System of Liaoning Medical University First Affiliated Hospital (LMUFAH) system from May 2015 to August 2016. Of them, 855 patients with completed data available were used in the analysis. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Serum amino acids were measured by mass spectrometry (MS) technology. Binary logistic regression was performed to obtain odds ratios (ORs) and their 95% confidence intervals (CIs). 52.3% of the 855 T2DM patients were male, and 143 had CKD. In univariable analysis, high serum citrulline, high ratio of arginine to ornithine, and low ratio of ornithine to citrulline were associated with markedly increased risk of CKD (OR of top vs. bottom tertile: 2.87, 95%CI, 1.79-4.62 & 1.98, 95%CI,1.25-3.14 & 2.56, 95%CI, 1.61-4.07, respectively). In multivariable analysis, the ORs of citrulline and ornithine/citrulline ratio for CKD remained significant (OR of top vs. bottom tertile: 2.22, 95%CI, 1.29-3.82 & 2.24, 1.29-3.87, respectively). In Chinese patients with T2DM, high citrulline and low ornithine/citrulline ratio were associated with increased risk of CKD.


Theranostics with multifunctional magnetic gold nanoshells: photothermal therapy and t2* magnetic resonance imaging.
to investigate the multifunctional imaging and therapeutic capabilities of core-shell nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and a gold shell (SPIO@AuNS). the magnetic/optical properties of SPIO@AuNS were examined both in an agar gel phantom and in vivo by evaluating contrast-enhanced magnetic resonance imaging (MRI) and by measuring near-infrared (NIR) light-induced temperature changes mediated by SPIO@AuNS. In addition, the biodistribution and pharmacokinetics of In-labeled SPIO@AuNS after intravenous injection in mice bearing A431 tumors were evaluated in the presence and absence of an external magnet. : In agar phantoms containing SPIO@AuNS, a significant contrast enhancement in T2-weighted MRI was observed and a linear increase in temperature was observed with increasing concentration and laser output power when irradiated with NIR light centered at an 808 nm. In vivo, T2*-MRI delineated SPIO@AuNS and magnetic resonance temperature imaging of the same tumors revealed significant temperature elevations when intratumorally injected with SPIO@AuNS (1 × 10 particles/mouse) and irradiated with NIR light (65.70°C ± 0.69°C vs. 44.23°C ± 0.24°C for saline + laser). Biodistribution studies in mice intravenously injected with In-labeled-SPIO@AuNS(1 × 10 particles/mouse) had an approximately 2-fold increase in SPIO@AuNS delivered into tumors in the presence of an external magnet compared with tumors without the magnet. owing to its ability to mediate efficient photothermal ablation of cancer cells under MRI guidance, as well as the ability to be directed to solid tumors with an external magnetic field gradient, multifunctional SPIO@AuNS is a promising theranostic nanoplatform.


Growth factors as novel therapeutic targets in neoplastic disease.
The emerging concept of autocrine/paracrine control of tumour cell proliferation coupled with the identification of several polypeptide mitogens has created new opportunities for the discovery of novel classes of antineoplastic drugs. Growth factors (for example, transforming growth factor alpha, fibroblast growth factor and platelet-derived growth factor) and, in certain cases, their receptors have been identified in a number of human tumours and their expression may contribute to unregulated cell proliferation. Selective antagonists that block the activity of these mediators may have important therapeutic utility in the management of cancer patients, particularly in metastatic disease where patterns of tumour cell dissemination may be strongly influenced by paracrine mediators. However, since many, if not all, of these growth factors are polypeptides with molecular weights over 5 kDa, the discovery of potent antagonists represents an important pharmacological challenge. Advances in understanding protein structure-function relationships will be essential in guiding rational attempts at generating growth factor antagonists through site-directed mutagenesis and peptide synthesis, while better insights into the mechanisms by which growth factors are synthesized, processed, released and exert their mitogenic effects may also reveal new sites for pharmacological assault. The availability of (low molecular weight) potent growth factor antagonists will allow the autocrine/paracrine hypothesis to be clinically tested and in the process will throw considerable light on the function of these growth regulatory molecules in vivo.


Pulpal response to different pulp capping methods after pulp exposure by air abrasion.
Air abrasion is regaining popularity especially in the area of pediatric dentistry due to its ease of use and its advantages. Due to the lost of tactile information, while using this technique, there is an increased risk for pulpal exposure. On the other hand, Ca(OH)2 medicament has been proven to induce dentin bridge formation, but an adequate sealing seems to be even more important that the capping material used. The purpose of this study was two fold: to assess the pulpal response after pulpal exposure by air abrasion and to evaluate the healing potential after using Ca(OH)2 medicament or Liner Bond II as a capping agent. Two hundred sixteen teeth from mixed-bred dogs were used in this study. The teeth were divided into three groups, A) pulpal exposure by air-abrasion followed by sealing of the cavity with Liner Bond II, B) pulpal exposure by air-abrasion and Ca(OH)2 pulp capping and C) pulpal exposure by high-speed followed by air-abrasion and Ca(OH)2 pulp capping as a control group. The animals were sacrificed after 7, 14, 30 and 60 days and a histopathological evaluation was undertaken. After applying Analysis of Variance to compare the groups, it was observed that at earlier observation periods, the inflammatory criteria near the exposure site were different among the groups. As time elapsed, the inflammation was resolved in the pulp tissue, however, the odontoblastic layer and the dentin bridge formation had a highly statistically significant difference (p<0.001) among the various groups at all observation periods. In addition, a positive correlation was observed between the organization of the odontoblastic layer and the dentin bridge formation mainly after 30 days. It could be concluded that dentin bridge formation could be achieved with the use of Ca(OH) or Liner Bond II as capping agent with an adequate sealing. However, the formation is delayed especially when Liner Bond II is used as capping agent.


The urethral syndrome and its management.
The urethral syndrome and its management are reviewed. Urethral syndrome is defined as 'symptoms suggestive of a lower tract urinary infection but in the absence of significant bacteriuria with a conventional pathogen' with three provisos concerning symptomatology and the definition of significant bacteriuria and conventional pathogens. The urethral syndrome is a very common condition; about half the patients visiting their General Practitioner by reason of frequency and/or dysuria do not have significant bacteriuria. Both infective causes (such as lactobacilli and sexually-transmitted pathogens) and non-infective causes (such as trauma, allergies, anatomical features and co-existing medical conditions) have been suggested as causes and are discussed. Treatment options include antibiotics in the case of acute urethral syndrome, since it is not possible to distinguish between urinary infection and the urethral syndrome in the consulting room. For those with chronic urethral syndrome, treatment depends upon whether attacks are associated with bacteriuria or if urological investigations reveal any abnormalities.


Transport proteins in rats' renal corpuscle and tubules.
The localization of transepithelial transport proteins for glucose and water reabsorption in renal corpuscle and tubules epithelium was observed. Immunohistochemistry of normal male Wistar rats' kidney has been performed. Facilitated diffusion glucose transporter GLUT4, Na(+)-dependent glucose co-transporter SGLT1, a cargo transporter TGN38, and water transporter aquaporin-2 (AQP2) were used. An intensive GLUT4 expression in renal proximal tubules and in convoluted segment of distal tubules has been observed. The intensive SGLT1 expression was marked in all renal tubules, and also in the glomerulus of the renal corpuscle. TGN38 was expressed mainly in the S1 of proximal tubules and a bit weaker in the distal tubules. The most intensive AQP2 expression in the proximal tubules and in the thin part of Henle's loop has been detected. In some cases AQP2 expression in the collecting tubules has been observed. The same tubules nephroni are marked heterogeneously. The distribution of transepithelial transport proteins in different parts of nephroni is also greatly heterogeneous because of weak determination of urinary system. The comparable transport-proteins distribution with technique of fluorescence immunohistochemistry in rats' renal corpuscle and tubules was elucidated. Data suggest that expression of glucose and water transepithelial transporter proteins is heterogeneous in all parts of nephron, and, probably, is in accordance with recycling of transport proteins.


High-Performance Transparent and Conductive Films with Fully Enclosed Metal Mesh.
Metal mesh films as a kind of transparent conductive electrodes (TCEs) have shown high promise in various optoelectronic devices but are still challenged by a combination of high conductivity and transparency, mechanical robustness, and uniform electric field. Herein, we demonstrate a new concept of transparent and conductive films with a fully enclosed metal mesh, which is embedded in deep microcavities and is coated with a conductive polymer layer to combine these metrics. To ensure high conductivity and transparency, metal ink is filled into the fine (down to submicrometers) and deep mesh microcavities by electrowetting-assisted blading with low square resistances of 0.4 and 2.69 Ω sq-1 at typical transmittances of 76.9 and 87.4%, respectively. The covered thin conductive polymer layer improves the electric field uniformity of metal mesh films by at least three orders of magnitude. The fully enclosed metal mesh films exhibit excellent mechanical flexibility, indicated by the fact that the resistance is almost unchanged after 10,000 bending cycles at a bending radius of ∼5 mm. Based on the fully enclosed metal mesh films, the emission intensity of alternating current electroluminescent devices is improved by more than three times compared with that in the case of solely using common metal mesh films.


Enolate-Azide [3 + 2]-Cycloaddition Reaction Suitable for DNA-Encoded Library Synthesis.
The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate-azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles. Thus, it will not only further enrich the DEL chemistry toolbox but also will have great potential in practical DEL synthesis.


Use of two selective media and a broth motility test can aid in identification or exclusion of Bacillus anthracis.
During the anthrax attack of 2001, the Florida Department of Health (FDOH) Bureau of Laboratories in Tampa received hundreds of isolates suspected of being Bacillus anthracis. None were confirmed to be B. anthracis since most isolates were motile and not even in the Bacillus cereus group. Although the sentinel laboratories now send fewer isolates to FDOH laboratories, should another attack occur the number of isolates submitted would likely increase dramatically, and this upsurge would seriously challenge personnel who are expected to be busy examining an increased number of environmental samples. We examined two selective and differential growth media and alternative motility methods that could be used to streamline the processing of suspicious isolates. Of 60 isolates previously sent to the FDOH laboratory, 56 were endospore-forming gram-positive rods and only 7 grew on mannitol-egg yolk-polymyxin B agar and/or the Anthracis chromogenic agar. Microscopic observation of early-log-phase growth (2 to 3 h) in a shaking broth was the best method to detect motility in 40 isolates that appeared nonmotile in the motility media investigated. One of these growth media and microscopic examination of shaken broth cultures can be used to show that an isolate is not B. anthracis before expensive molecular and antibody-based tests are performed. By doing so, costs could be reduced and analysis time shortened.


Nanotopographic Influence on the In Vitro Behavior of Induced Pluripotent Stem Cells.
While the influence of nanotopography on stem cell behavior has been extensively investigated on adult stem cells, far fewer studies have investigated the interaction of induced pluripotent stem cells (iPSCs) with various nanotopographical patterns. The purpose of this study was to identify nanopatterns that can influence the stemness and proliferation, as well as the adhesive properties in iPSCs, and thereby explore the feasibility of applying these nano-features for regenerative medicine. Three kinds of nanopatterns were fabricated from polydimethylsiloxane membranes, irregular patterned membrane (IPM), groove patterned membrane (GPM), and postpatterned membrane (PPM), in addition to flat patterned membrane (FPM) which did not have any nanotopographic features and was used as the control pattern. On the surfaces of GPM or PPM, iPSCs showed tendency for aggregation and did not spread out well at passage 1. However, with continued passaging (P6, P10), the tendency to form aggregates was greatly reduced. While iPSCs cultured on GPM and PPM had low population doubling time values compared with FPM and IPM at P1, the differences disappeared in later passages. The expression of the cell proliferation marker Ki67 in iPSCs gradually decreased with continued passaging in cells cultured on FPM and IPM, but not in those cultured on GPM and PPM. The expression of Oct3/4 and Nanog, marker of stemness, was significantly higher on GPM and PPM than on FPM at P6 and P10. At P5, numerous filopodia were demonstrated in the peripheral attachments of iPSC colonies on FPM and IPM, while GPM and PPM generally had globular appearance. The expression of the focal adhesion (FA) molecules α-actinin, vinculin, phalloidin, or FA kinase was significantly greater on GPM and PPM than on FPM and IPM at P6 or P10. In conclusion, continued passaging on regular nanopatterns, including groove- and post-forms, was effective in maintaining an undifferentiated state and proliferation of iPSCs and also in increasing the expression of FA molecules.


Fructose consumption in the Netherlands: the Dutch National Food Consumption Survey 2007-2010.
Despite the worldwide scientific and media attention, the actual fructose consumption in many non-US populations is not clear. The aim of this study was to estimate the fructose consumption and its main food sources in a representative sample of the general Dutch population. In all, 3817 children and adults aged 7-69 years from the Dutch National Food Consumption Survey 2007-2010 were studied. Values for fructose content of the products were assigned using several food composition tables. Diet was assessed with two nonconsecutive 24-h dietary recalls. The Multiple Source Method was used to take into account day-to-day variation and to estimate the habitual fructose consumption. Median habitual fructose intake was 46 g/day, with an interquartile range of 35-60 g/day. In boys, the highest median intake was observed among 14- to 18-year olds: 61 g/day. In girls, those aged 9-13 years reported the highest median intake: 56 g/day. Of total fructose intake, 67% was consumed in the form of sucrose and 33% was consumed as free fructose. Soft drinks constituted the main food source of total fructose (13-29% across age and sex categories), followed by juices (9-12%), fruit (9-18%), cake and cookies (9-11%) and dairy products (6-10%). Fructose comprised 9% of the mean daily energy intake in the general Dutch population aged 7-69 years. The fructose consumption was somewhat lower than most recent figures from the US. The main food sources of fructose were soft drinks, juices and fruit.


[What General/Family Medicine Practitioner should Know about Viral Hepatitis].
Viral hepatitis is a systemic disease that predominantly affects the liver. The most common causes of viral hepatitis are fi ve hepatotropic viruses A, B, C, D and E; according to duration, it can be acute or chronic. Although clinical course of all viral hepatitides is similar, particular problem is predisposition of hepatitis B and hepatitis C to cause chronic forms of illness with severe outcome such as cirrhosis, hepatocellular carcinoma and liver failure. Clinical features include malaise, nausea, anorexia, low grade fever, aversion to smoking, and in clinical status usually we can fi nd hepatomegaly, and seldom splenomegaly with adenopathy and jaundice. Generally, symptoms are very variable, from usually asymptomatic to fulminant, which in most cases have lethal outcome. There are three stages in acute phase of viral hepatitis: prodromal, icteric and convalescence. Standard laboratory tests show elevated values of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in acute phase of hepatitis and elevated lactate dehydrogenase in chronic phase. Serum protein electrophoresis usually shows decreased albumin fraction and albumin/globulin ratio, as well as increased bilirubin level, positive urobilinogen and disturbance in coagulability factors, i.e. marked prolongation of prothrombin time. For etiology of each virus, series of serologic tests are used. In hepatitis A, acute phase of disease is characterized by IgM anti-HAV and presence of IgG anti-HAV indicates previous exposure. In hepatitis B, appearance of HBsAg in serum is the fi rst evidence of infection and recovery is connected with appearance of anti-HBsAg along with IgG anti HBcAg. Active forms of chronic hepatitis B are characterized by active virus replication, which can be measured with polymerase chain reaction (PCR) HBV DNA. Diagnosis of hepatitis C is based on detection of antibodies to HCV (anti-HCV). Generally, it signifi es that HCV infection is present but that diagnostic tool is poor for the phase of disease. In these circumstances, diagnosis of hepatitis C may be confi rmed by using an assay for HCV RNA. First line therapy in acute phase is mostly supportive, i.e. bed rest, appropriate diet including palatable meals as tolerated, without overfeeding. Alcohol and hepatotoxic agents (for example, paracetamol, amoxicillin, ketoconazole) should be avoided. In cases with increased tendency of developing chronic forms of hepatitis and complications (cirrhosis, hepatocellular carcinoma), immunomodulators should be administered, e.g., interferon and/or antiviral agents. The role of family physician/general practitioner is in maintaining preventive measures (vaccination) and education of general population. Special attention needs to be paid to screening and educating high risk patients with respect to proper diagnostics, laboratory and serologic tests. After establishing the diagnosis, all relevant measures should be taken to avoid chronifi cation of disease. In case of chronic hepatitis, consultation with infectious disease specialist and/or gastroenterologist is needed in the treatment and follow up of the patient.


Multifeature-based surround inhibition improves contour detection in natural images.
To effectively perform visual tasks like detecting contours, the visual system normally needs to integrate multiple visual features. Sufficient physiological studies have revealed that for a large number of neurons in the primary visual cortex (V1) of monkeys and cats, neuronal responses elicited by the stimuli placed within the classical receptive field (CRF) are substantially modulated, normally inhibited, when difference exists between the CRF and its surround, namely, non-CRF, for various local features. The exquisite sensitivity of V1 neurons to the center-surround stimulus configuration is thought to serve important perceptual functions, including contour detection. In this paper, we propose a biologically motivated model to improve the performance of perceptually salient contour detection. The main contribution is the multifeature-based center-surround framework, in which the surround inhibition weights of individual features, including orientation, luminance, and luminance contrast, are combined according to a scale-guided strategy, and the combined weights are then used to modulate the final surround inhibition of the neurons. The performance was compared with that of single-cue-based models and other existing methods (especially other biologically motivated ones). The results show that combining multiple cues can substantially improve the performance of contour detection compared with the models using single cue. In general, luminance and luminance contrast contribute much more than orientation to the specific task of contour extraction, at least in gray-scale natural images.


Fracture Resistance of Different Designs of a Resin-Bonded Fixed Dental Prosthesis: An In Vitro Study.
To evaluate the effect of three two-retainer designs of a resin-bonded fixed dental prosthesis (RBFDP) on fracture resistance. A total of 21 three-unit, all-ceramic RBFPDs were fabricated to replace a missing maxillary lateral incisor. The prostheses were divided into three groups of 7 each: Group L (labial RBFPD); Group ML (modified labial RBFPD, fabricated the same as in Group L with additional preparation that included a shallow proximal groove at the pontic side); and Group P, an all-ceramic palatal RBFPD that acted as control. Preparations were done on the maxillary left central incisor and canine of a typodont model, and 21 epoxy resin models were duplicated for the three groups. The RBFPDs were designed using CAD software and constructed using the heat-pressed technique, after which the prostheses were bonded to their corresponding epoxy resin model according to the manufacturer's instructions. A fracture resistance test was performed on all specimens following aging. Data were analyzed using one-way ANOVA. The highest fracture load values were recorded in Group P (547.5 N), followed by Group ML (462.6 N) and then Group L (418.3 N). The difference among the three designs was not statistically significant (F = 2.5, P = 0.1). Both labial and modified labial RBFDPs could be a viable alternative treatment option for replacement of missing maxillary lateral incisors.


Active site labeling of G8 in the hairpin ribozyme: implications for structure and mechanism.
There is mounting evidence that suggests that general acid/base catalysis is operative in the hairpin ribozyme, with analogy to the protein enzyme RNaseA. Nevertheless, the extent of general base catalysis as well as the identity of the specific chemical groups responsible remains the subject of some controversy. An affinity label has previously been used to alkylate histidine 12 (His12), the active general base in RNaseA. To date, no such experiment has been applied to a ribozyme. We have synthesized the analogous affinity label for the hairpin ribozyme with an electrophilic 2'-bromoacetamide group in lieu of the 2'-hydroxyl (2'OH) at the substrate cleavage site and show that guanosine 8 (G8) of the hairpin ribozyme is specifically alkylated, most likely at the N1 position. This evidence strongly implicates N1 of G8 in active site chemistry. By direct analogy to RNase A, these findings could be consistent with the hypothesis that deprotonated G8 residue functions as a general base in the hairpin ribozyme. Other mechanistic possibilities for N1 of G8 such as indirect general base catalysis mediated by a water molecule or transition state stabilization could also be consistent with our findings.


Anatomic anterior cruciate ligament reconstruction with a flexible reamer system and 70° arthroscope.
Anterior cruciate ligament (ACL) reconstruction techniques continue to evolve as surgeons seek to improve surgical process and outcome measures. On the basis of published data showing improved biomechanics, many surgeons now attempt to better re-create native ACL anatomy in reconstruction. Use of flexible reamer technology and a 70° arthroscope allows for excellent visualization of the native ACL anatomy, as well as precise and independent drilling of the tibial and femoral reconstruction tunnels, while offering several surgical and technical advantages compared with other drilling techniques. This technical note with accompanying video describes our use of the Smith & Nephew Clancy anatomic cruciate guide/flexible drill system (Smith & Nephew, London, England) with a 70° arthroscope.


Induction of impaired activation of lymphocytes by suppressive factor in Crohn's disease patients.
Lymphocyte proliferative response to phytohemagglutinin (PHA) and relevance of serum factors to the response were studied in 12 patients with Crohn's disease (CD). The lymphocyte proliferative response was markedly reduced in patients with Crohn's disease (S.I. = 38.8 +/- 36.8) (mean +/- SD), as compared with normal controls (S.I. = 100.6 +/- 28.6) (p less than 0.01). In addition, the effect of sera from patients with CD or 10 patients with ulcerative colitis (UC) who had extremely impaired lymphocyte responsiveness to PHA on the proliferative response of normal lymphocytes to PHA was also measured. Sera from CD patients had a marked suppressive effect on the blastogenesis of normal lymphocytes (S.I. = 46.4 +/- 28.5), as compared with normal sera (S.I. = 126.2 +/- 14.7) (p less than 0.001). On the other hand, UC sera did not suppress the blastogenesis of normal lymphocytes (S.I. = 114.9 +/- 27.7). Moreover, serum immunosuppressive acidic protein (IAP) levels in patients' sera were measured by single radial immunodiffusion assay. A marked increase in serum IAP levels was revealed both in CD patients (780 +/- 470 micrograms/ml) and in UC patients (601 +/- 278 micrograms/ml), as compared with normal controls (376 +/- 92 micrograms/ml) (p less than 0.001). But there was no precise correlation between the suppressive effect of sera and serum IAP levels in patients with CD. Thus, we demonstrated an impairment of the lymphocyte responsiveness to PHA in CD patients and the possible existence of immunosuppressive factors which is not identical with IAP in the sera from patients with CD.


The driving effects of nitrogen deposition on nitrous oxide and associated gene abundances at two water table levels in an alpine peatland.
Alpine peatlands are recognized as a weak or negligible source of nitrous oxide (N2O). Anthropogenic activities and climate change resulted in the altered water table (WT) levels and increased nitrogen (N) deposition, which could potentially transition this habitat into a N2O emission hotspot. However, the underlying mechanism related with the effects is still uncertain. Hence, we conducted a mesocosm experiment to address the response of growing-season N2O emissions and the gene abundances of nitrification (bacterial amoA) and denitrification (narG, nirS, norB and nosZ) to the increased N deposition (20 kg N ha-1 yr-1) at two WT levels (WT-30, 30 cm below soil surface; WT10, 10 cm above soil surface) in the Zoige alpine peatland, Qinghai-Tibetan Plateau. The results showed that the WT did not affect N2O emissions, and this was attributed with the limitation of soil NO3-. The higher WT level increased denitrification (narG and nirS gene abundance) resulting in the depletion of soil NO3-, but the consequent NO3- deficiency further limited denitrification, while the WT did not affect nitrification (bacterial amoA gene abundance). Meanwhile, the N deposition increased N2O emissions, regardless of WT levels. This was associated with the N-deposition induced increase in denitrification-related gene abundances of narG, nirS, norB and nosZ at WT-30 and narG at WT10. Additionally, the N2O emission factor assigned to N deposition was 1.3 % at WT-30 and 0.9 % at WT10, respectively. Our study provided comprehensive understanding of the mechanisms referring N2O emissions in response to the interactions between climate change and human disturbance from this high-altitude peatland.


17β Estradiol Modulates Perfusion Pressure and Expression of 5-LOX and CYP450 4A in the Isolated Kidney of Metabolic Syndrome Female Rats.
Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF-α were increased in ovariectomized metabolic syndrome rats (p < 0.001). The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 μg of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways.


DLG2 intragenic exonic deletions reinforce the link to neurodevelopmental disorders and suggest a potential association with congenital anomalies and dysmorphism.
Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed additional studies to confirm this clinical association and DLG2 haploinsufficiency. Chromosomal microarray analysis was performed on 11,107 patients at the Cytogenetics Laboratory at the University of Alabama at Birmingham. The Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database were selected for the association analysis. Fifty-nine patients from the literature and DECIPHER, all having DLG2 intragenic deletions, were included for comprehensive analysis of the distribution of these deletions. A total of 13 patients with DLG2 intragenic deletions, from 10 families in our cohort, were identified. Nine of 10 probands presented with clinical features of neurodevelopmental disorders. Congenital anomalies and dysmorphism were common in our cohort of patients. Association analysis showed that the frequency of DLG2 deletions in our cohort is significantly higher than those in the Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database. Most of DLG2 intragenic deletions identified in 69 unrelated patients from our cohort, the literature, and DECIPHER map to the 5' region of the gene, with a hotspot centered around HPin7, exon 8, and HPin8. Our findings reinforce the link between DLG2 intragenic deletions and neurodevelopmental disorders, strongly support the haploinsufficiency of this gene, and indicate that these deletions might also have an association with congenital anomalies and dysmorphism.


Deep Learning-Aided Inertial/Visual/LiDAR Integration for GNSS-Challenging Environments.
This research develops an integrated navigation system, which fuses the measurements of the inertial measurement unit (IMU), LiDAR, and monocular camera using an extended Kalman filter (EKF) to provide accurate positioning during prolonged GNSS signal outages. The system features the use of an integrated INS/monocular visual simultaneous localization and mapping (SLAM) navigation system that takes advantage of LiDAR depth measurements to correct the scale ambiguity that results from monocular visual odometry. The proposed system was tested using two datasets, namely, the KITTI and the Leddar PixSet, which cover a wide range of driving environments. The system yielded an average reduction in the root-mean-square error (RMSE) of about 80% and 92% in the horizontal and upward directions, respectively. The proposed system was compared with an INS/monocular visual SLAM/LiDAR SLAM integration and to some state-of-the-art SLAM algorithms.


Effect of TGF-beta 1 on re-epithelialization of human keratinocytes in vitro: an organotypic model.
Transforming growth factor beta-1 (TGF-beta 1) has been shown to inhibit keratinocyte proliferation in vitro yet and migration was investigated in organotypic cultures after incisional wounding. Organotypic cultures provide a more in vivo-like epidermal tissue and may therefore respond in a different manner than previous culture models in which epidermal differentiation is incomplete. Without TGF-beta 1, keratinocytes were hyperproliferative in response to wounding. At doses of 2.5 ng/ml or greater, a delay in re-epithelialization was seen at 24 h post-wounding along with a reduction in hyperproliferation. By 48 h, however, re-epithelialization was complete in all cultures treated with TGF-beta 1. In particular, 7 ng/ml TGF-beta 1 inhibited proliferation yet had no effect on re-epithelialization by 48 h. These studies demonstrate that i) TGF-beta 1 induced a delay in re-epithelialization, ii) proliferation of wounded keratinocytes was not inhibited at 2.5 ng/ml doses of TGF-beta 1, and iii) at 7 ng/ml TGF-beta 1, re-epithelialization was complete by 48 h in spite of the profound inhibition of cell proliferation. In the organotypic model, TGF-beta 1 appears to alter re-epithelialization.


Vitis vinifera leaf extract liposomal Carbopol gel preparation's potential wound healing and antibacterial benefits: in vivo, phytochemical, and computational investigation.
Vitis vinifera Egyptian edible leaf extract loaded on a soybean lecithin, cholesterol, and Carbopol gel preparation (VVL-liposomal gel) was prepared to maximize the in vivo wound healing and anti-MRSA activities for the crude extract, using an excision wound model and focusing on TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1β, and MRSA (wound infection model, and peritonitis infection model). VVL-liposomal gel was stable with significant drug entrapment efficiency reaching 88% ± 3, zeta potential value ranging from -50 to -63, and a size range of 50-200 μm nm in diameter. The in vivo evaluation proved the ability of VVL-liposomal gel to gradually release the drugs in a sustained manner with greater complete wound healing effect and tissue repair after 7 days of administration, with a significant decrease in bacterial count compared with the crude extract. Phytochemical investigation of the crude extract of the leaves yielded fourteen compounds: two new stilbenes (1, 2), along with twelve known ones (3-14). Furthermore, a computational study was conducted to identify the genes and possible pathways responsible for the anti-MRSA activity of the isolated compounds, and inverse docking was used to identify the most likely molecular targets that could mediate the extract's antibacterial activity. Gyr-B was discovered to be the best target for compounds 1 and 2. Hence, VVL-liposomal gel can be used as a novel anti-dermatophytic agent with potent wound healing and anti-MRSA capacity, paving the way for future clinical research.


Comparison of leukocyte count and function in smoking and nonsmoking young men.
Leukocyte function and other hematological measurements were tested in 14 smoking and 13 nonsmoking young men free of intercurrent or chronic diseases. Leukocyte chemotaxis was depressed in smoking subjects when compared to the same subjects abstaining from cigarettes or to the nonsmokers. Smoking did not affect the whole blood bactericidal capacity of leukocytes and serum for Staphyloccus aureus or Klebsiella pneumoniae. Total leukocyte counts, hematocritis, and monocyte counts were higher in the smoking subjects when compared to the nonsmokers.


Development of a portable therapeutic and high intensity ultrasound system for military, medical, and research use.
We have developed a portable high power ultrasound system with a very low output impedance amplifier circuit (less than 0.3 Omega) that can transfer more than 90% of the energy from a battery supply to the ultrasound transducer. The system can deliver therapeutic acoustical energy waves at lower voltages than those in conventional ultrasound systems because energy losses owing to a mismatched impedance are eliminated. The system can produce acoustic power outputs over the therapeutic range (greater then 50 W) from a PZT-4, 1.54 MHz, and 0.75 in diameter piezoelectric ceramic. It is lightweight, portable, and powered by a rechargeable battery. The portable therapeutic ultrasound unit has the potential to replace "plug-in" medical systems and rf amplifiers used in research. The system is capable of field service on its internal battery, making it especially useful for military, ambulatory, and remote medical applications.


Experience With High-Volume Buttock Fat Transfer: A Report of 137 Cases.
Buttock augmentation with fat transfer has become increasingly popular, with many patients seeking high-volume augmentations. Consensus is lacking as to the safe upper-limit of fat that can be transferred. Concern for risks such as fat necrosis and fat embolism may lead surgeons to limit the amount of fat to place. However, it is unclear if volume alone is associated with these complications. The author evaluated the outcomes of high-volume fat transfer. The author sought to evaluate the safety and efficacy of high-volume buttock fat transfer. A retrospective case review of all buttock fat transfers performed between 2014 and 2016 involving placement of 1000 mL or more per buttock was undertaken. Patients were monitored clinically and evaluated for their subjective assessment of satisfaction. A total of 137 patients were identified. A mean of 1331 mL of fat was placed in each buttock (range, 1000-1890 mL) and the mean age was 35.3 years (range, 19-56 years). One hundred eighteen patients (86.1%) were satisfied with their result. None complained of the buttocks having been made too large. Nineteen patients (13.9%) wanted the buttocks made larger. Eight patients underwent an additional fat transfer procedure. Twelve patients (8.8%) had minor cosmetic issues following surgery. Another 10 patients (7.3%) had minor medical complications. No patient suffered major complications such as fat embolism, venous thromboembolism, infection, or skin loss. High-volume buttock fat transfer is safe and effective in increasing the buttock volume. Complication rates appear to be low with careful surgical technique. No serious complications were noted in this case series.


[Giovanni Dondi dall'Orologio's "Astrario" and the astrologic science in the Middle Ages].
The large room of the Paduan "Palazzo della Ragione" (The Hall of Reason) has exhibited "padua sidus preclarum": Dondi dall'Orologio and Padua of Carraresi. All the exhibition centers on the evidence of the main and irreplaceable presence which astrology had in the social life of the Middle Ages. Among other things, the show presents the faithful reconstruction of Giovanni Dondi's "astrario", a complicated astronomic-astrologic "time-piece".


Locomotion in captive Leontopithecus and Callimico: a multimedia study.
Video studies, gait analysis, footprint tracks, and observational scan sampling show that, in comparably furnished enclosures, Leontopithecus rosalia and Callimico goeldii are superficially similar in their use of predefined locomotor patterns but differ profoundly in many underlying details which reflect differences in postcranial morphology. Each uses pronograde arboreal quadrupedal walking, quadrupedal bounding, and vertical climbing with comparable frequency, and both shift to bounding while moving quadrupedally at high speeds. In walking, both species use a diagonal sequence gait. However, in Callimico the distance per bout traveled while walking or running is shorter than in L. rosalia and there is an emphasis on leaping (from a stationary position) and bounding-leaps (saltational extensions of pronograde quadrupedalism), in contrast with the basically quadrupedal style of L. rosalia. This dichotomy is consistent with anatomical specializations, such as forelimb elongation in Leontopithecus and hindlimb elongation in Callimico. In vivo hand- and footprint studies demonstrate grasping halluces in both species while walking. Limb stances in L. rosalia during "transaxial bounding" involve an overstriding hindlimb, a predominance of oblique rather than in-line travel, and unique hand and foot positions. Anatomically, this locomotor style may be associated with reduced dexterity of the elongate hands and a relatively short hallux. The captive locomotor profiles for both species probably reflect biased samples of the locomotor repertoire of their wild counterparts. Nevertheless, these data reflect species-specific integrations of locomotor behavior and morphology, and corroborate expectations of locomotor diversity among callitrichine primates, even those of similar body size. It is suggested, however, that conventional quantitative studies of locomotor profiles may prove inadequate for resolving subtle aspects of locomotor morphology and behavior.


Do disability grants influence adherence to antiretroviral therapy?
Anecdotal data suggest that some South Africans living with HIV who receive disability grants from the state deliberately default on their antiretroviral medication in an attempt to lower their CD4 count to remain eligible for grants. No actual empirical data however exist to show that disability grants act as such perverse incentives and are a valid reason for non-adherence. This article examines some of the complexities of antiretroviral adherence in the context of a resource-constrained environment. The multitude of structural barriers, including sometimes difficult patient-doctor conversations about the renewal of disability grants, shape patients' experiences of the clinic environment and influence their adherence to care.


International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.
Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1-9) and a soluble AC (sAC, also referred to as AC10). This review will largely focus on mACs. mACs are activated by the G-protein Gαs and regulated by multiple mechanisms. mACs are differentially expressed in tissues and regulate numerous and diverse cell functions. mACs localize in distinct membrane compartments and form signaling complexes. sAC is activated by bicarbonate with physiologic roles first described in testis. Crystal structures of the catalytic core of a hybrid mAC and sAC are available. These structures provide detailed insights into the catalytic mechanism and constitute the basis for the development of isoform-selective activators and inhibitors. Although potent competitive and noncompetitive mAC inhibitors are available, it is challenging to obtain compounds with high isoform selectivity due to the conservation of the catalytic core. Accordingly, caution must be exerted with the interpretation of intact-cell studies. The development of isoform-selective activators, the plant diterpene forskolin being the starting compound, has been equally challenging. There is no known endogenous ligand for the forskolin binding site. Recently, development of selective sAC inhibitors was reported. An emerging field is the association of AC gene polymorphisms with human diseases. For example, mutations in the AC5 gene (ADCY5) cause hyperkinetic extrapyramidal motor disorders. Overall, in contrast to the guanylyl cyclase field, our understanding of the (patho)physiology of AC isoforms and the development of clinically useful drugs targeting ACs is still in its infancy.


Functional outcome after inpatient rehabilitation in persons with subarachnoid hemorrhage.
To describe inpatient rehabilitation outcome in persons with nontraumatic subarachnoid hemorrhage (SAH) and to explore the predictive capacity of acute measures of SAH severity and demographic and disease variables. Retrospective with descriptive and relational analyses. Free-standing, acute, inpatient brain injury rehabilitation unit. Forty-two consecutive persons with nontraumatic SAH and for whom complete data were available were studied. Mean age of the group was 56.5 years, mean acute hospital stay was 26.2 days, and 60% were women. Over 40% experienced rupture of an anterior communicating artery aneurysm. The time from injury to rehabilitation admission varied from 11 to 227 days (mean, 43.8d). Not applicable. Change in FIMtrade mark instrument scores, home discharge rate, and rehabilitation length of stay (LOS.) The mean admission and discharge FIM scores were 57.7 and 85.5 points, respectively. There was a 27.8-point mean change in FIM score over a 24.1-day mean rehabilitation LOS for a FIM efficiency (points/day) of 1.15. Over 80% of the sample was discharged home. No demographic or disease characteristic variables, including acute severity measures, were statistically significant predictors of outcome. Functional gains during inpatient rehabilitation made in this group of 42 persons with SAH are in line with earlier studies. Our rehabilitation LOS is the shortest reported among 4 studies to date and is probably a reflection of managed care in the United States. A small sample, uneven cell sizes, and variability of patients might have contributed to a lack of significant findings. Future study should explore the prediction of rehabilitation outcome using larger sample sizes and longer follow-up periods.


US Health Resource Utilization and Cost Burden Associated with Choroideremia.
Choroideremia is a progressive, inherited retinal dystrophy that leads to blindness. This study of choroideremia addresses health resource utilization (HRU) and costs from a US payor perspective using insurance claims data. The retrospective analysis used data between January 2013 and December 2018 from the IBM MarketScan Commercial, Medicare Supplemental, and Multi-State Medicaid Databases. Patients having ≥1 claim with an International Classification of Diseases, Ninth or Tenth Edition, diagnostic code for choroideremia (363.55/H31.21) were included; a control group was matched 3:1 to the choroideremia group. Patients were followed for ≥6 months. All-cause HRU and costs were compared between cohorts using generalized linear models adjusted for Charlson Comorbidity Index. There were 199 and 597 patients in the choroideremia and control groups, respectively; the choroideremia group had a higher mean baseline Charlson Comorbidity Index (0.47 vs 0.26). The choroideremia group had a significantly greater mean number of hospital admissions (0.09 vs 0.06), outpatient visits (22.33 vs 11.22), and emergency department visits (0.41 vs 0.26) per patient per year than the control group. The choroideremia cohort had higher all-cause total annualized costs than the control cohort ($15,372 vs $9285), primarily driven by outpatient visits ($8306 vs $4702). This trend was observed across age categories, particularly among patients aged 20 to 44 years (choroideremia, $14,544 vs control, $5953). The choroideremia group had higher all-cause HRU and total costs versus the control group. These findings provide economic context around HRU associated with choroideremia and help assess the potential impact of novel treatments.


Regional vascular resistance and haemodynamics in the spontaneously hypertensive rat: the effects of bradykinin.
To identify those vascular beds that contribute to the elevated peripheral resistance (TPR) seen in spontaneously hypertensive rats (SHR) as compared to Wistar-Kyoto rats (WKY), the distribution of cardiac output, organ blood flow, and regional vascular resistance were measured using radiolabelled microspheres. WKY and SHR had similar heart rates, cardiac outputs, and cardiac stroke volumes, whereas SHR had significantly elevated TPR. This increased TPR was the cumulative effect of significant elevations in vascular resistance in the brain, testes, epididymides, gastrointestinal tract, pancreas/mesentery, skin, kidneys, and skeletal muscle. Only in the renal and skeletal muscle vasculature was this elevation in resistance associated with reduced blood flow. Haemodynamic responses to bradykinin [thought to act through a release of endothelium-derived relaxing factor (EDRF)] were similar in both WKY and SHR with the exception of the liver where no reduction of hepatic arterial resistance was seen in the SHR. We suggest that the increase in resistance in the renal and skeletal muscle vasculature is due to active vasoconstriction in these beds. This vasoconstriction diverts a significant proportion of the cardiac output through other vascular beds, especially the brain, liver, and coronary circulation. This will result in increased shear-stress and consequent damage to endothelial cells.


A bifunctional Lewis acid induced cascade cyclization to the tricyclic core of ent-kaurenoids and its application to the formal synthesis of (±)-platensimycin.
A mild and efficient bifunctional Lewis acid induced cascade cyclization reaction has been developed for construction of the tricyclic core of ent-kaurenoids. With ZnBr(2) as the bifunctional Lewis acid, a series of substituted enones and dienes underwent cascade cyclization smoothly at room temperature and provided the tricyclic products in one pot with good yields (75-91%) and high diastereoselectivity. The cyclized product has been successfully employed for the formal synthesis of (±)-platensimycin.


[Not Available].
Complex relations between Chinese and western medicine are discussed: disease is considered as general omeostatic alteration of the whole organism. Nowadays the two medicines should integrate owing to the different methods of analysis of the patient. Acupuncture in its complex techniques, pharmacology and dietology are able to respond to health problems of single patients.


Risk factors for recurrent severe anemia among previously transfused children in Uganda: an age-matched case-control study.
In resource-poor settings, transfused children often experience recurrence of severe anemia (SA) following discharge from hospital. This study determined the factors associated with recurrent severe anemia (RSA) among previously transfused Ugandan children aged less than 5 years. A case-control study was conducted in five hospitals in Uganda from March 2017 to September 2018. We prospectively enrolled 196 hospitalised children who had been transfused for severe anemia 2 weeks to 6 months prior to enrollment. Of these, 101 children (cases) were re-admitted with a hemoglobin [Hb] level of ≤6 g/dL and required transfusion; and 95 children (age-matched controls) were admitted for other clinical illness with a Hb > 6 g/dL. Children known to have sickle cell anemia, cancer, or bleeding disorders were excluded. Clinical and laboratory evaluation were done. Conditional logistic regression adjusted for age, was used to determine factors associated with RSA. The median time (IQR) between the earlier transfusion and enrollment was 3.5 (1.9-5.7) months for cases, and was 5.0 (2.9-6.0) months for controls (p-value = 0.015). Risk factors (adjusted odds ratio, 95% confidence interval, and significance) for development of RSA were: hemoglobinuria (36.33, 2.19-600.66, p = 0.012); sickle cell anemia - newly diagnosed (20.26, 2.33-176.37, p = 0.006); history of earlier previous transfusions (6.95, 1.36-35.61, p = 0.020) and malaria infection (6.47, 1.17-35.70, p = 0.032). Malaria chemoprevention, follow up visit for Hb check after discharge from hospital and sickle cell screening among previously transfused children represent practical strategies to prevent and identify children at risk for recurrent severe anemia. The cause of hemoglobinuria in children merits further investigations.


Cytotoxic constituents of Baccharis gaudichaudiana.
Three new labdane diterpenes, gaudichaudols A-C [1-3], a new clerodane diterpenoid, gaudichaudone [4], and the known clerodane, articulin acetate [5] have been isolated from the aerial parts of Baccharis gaudichaudiana, together with the known compounds, apigenin, hispidulin, spathulenol, and ursolic acid. Through the application of 1D- and 2D nmr spectroscopy, the structures of the new diterpenoids [1-4] were, in turn; elucidated as 15,16,18,19-tetrahydroxylabd-5-ene, 15-O-acetyl-16,18,19-trihydroxylabd-5-ene, 16-O-p-trans-coumaroyl-15,18,19-trihydroxylabd-5-ene, and 2 beta-hydroxy-15,16-epoxycleroda-1(10),15,16-trien-18,19-olide++ +. The isolated compounds were evaluated in P-388 lymphocytic leukemia cells as well as a battery of human cancer cell lines. Among the diterpenoids, gaudichaudol C [3], gaudichaudone [4], and articulin acetate [5] exhibited significant cytotoxic activity against certain cancer cells.


Experimental demonstration of a dynamic range enhancement method for a phase-shifted PADC by using a modulo operation.
We propose what we believe to be a novel approach to enhance the dynamic range of a photonic analog-to-digital converter (PADC) without the need of additional custom-designed circuits or components. The method utilizes the unique characteristic of our previously reported multimode interference (MMI) coupler-based optical quantizer that exploits the periodicity of the optical phase to realize a modulo operation. Experiments were carried out to verify the effectiveness of the proposed method on our phase-shifted optical quantization ADC (PSOQ-ADC) chip. Experimental results show that our proposed method enhance the dynamic range from [-V π, V π] to [-2V π, 2V π] and has the potential to be further extended. Additionally, we successfully reconstructed radio frequency (RF) signals at a sampling rate of 30 Gs/s. Our work provides a promising solution for achieving a high dynamic range in on-chip PSOQ-ADC.


Restoring Connectedness in and to Nature: Three Nordic Examples of Recontextualizing Family Therapy to the Outdoors.
Mentalization-based family therapy and family rehabilitation represent a rich variety of approaches for assisting families with difficult interaction patterns. On the other hand, adventure therapy methods have been successfully used with families to offer them empowering experiences of succeeding together against difficult odds and to improve communication between family members. Further, the health promoting qualities of spending time outdoors are now well established and recognized. The Nordic approach to mentalization-based family rehabilitation combines adventure, outdoor, and systemic therapy. We provide three examples of nature-based family rehabilitation practices that are delivered as brief, multi-family psychological interventions taking place in nearby nature and aiming to support sustainable, systemic change. The current contribution is a description of clinical practice, not a systematic review or a formal evaluation. We propose that recontextualizing mentalization-based family rehabilitation to the outdoors can not only provide added health benefits, but also strengthen intra-familial attuned interaction and emotional connectedness. The outdoor adventure provides the families with embodied, multisensory experiences of verbal and, especially, non-verbal interaction that can be usefully examined through the lens of theory of mentalization. The concreteness of adventure experiences is particularly beneficial for families that have difficulties in verbal communication and/or utilizing executive functions, perhaps due to neuropsychiatric traits, intellectual disabilities, or learning difficulties. Furthermore, outdoor adventure can support the participants' connectedness to nature.


Impact of a patient education program on adherence to HIV medication: a randomized clinical trial.
Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.


The experience of symptoms and information needs of cancer patients undergoing radiotherapy.
The aim was to determine the symptoms and information needs of cancer patients undergoing radiotherapy (RT). The study population consisted of 345 RT patients accrued over 6 months. Patients' needs for information, sources of information, levels of satisfaction with information, symptoms and demographic factors were assessed by questionnaire and personal interview. Chi-square tests were used to test the correlation between patient variables and information needs/experiences. Most patients (80.9%) experienced RT side effects--fatigue, nausea, vomiting and loss of appetite were the most frequent. More than half of the patients had not received information about RT; however, patients (83.2%) who had problems during the treatment wanted to have information (P < 0.05). The majority of the patients receiving information identified doctors as the primary source. The patients' prioritized needs for information were all the aspects of their diagnosis and treatment and side effects of RT. Overall, the results indicate that most patients require information about their treatment and also experienced a variety of symptoms.


Interaction-controlled HPLC for block copolymer analysis and separation.
An interaction-controlled HPLC technique has been developed to analyze homopolymer precursors in block copolymer systems that are not easily identified by size exclusion chromatography (SEC) and to obtain block copolymers that are homopolymer-free and compositionally narrower than the as-synthesized ones. We demonstrate that a "single peak" in SEC does not necessarily mean that the block copolymers are free of homopolymers (due to limitations in the SEC analysis of block copolymers) and propose to employ the interaction-controlled HPLC strategy for rigorous analysis and purification of block copolymers in terms of their chemical heterogeneity.


A high macrophage content in human breast cancer is not associated with favourable prognostic factors.
The macrophage contents of 40 human primary breast cancers were ascertained using three separate macrophage membrane markers. Four prognostic factors (lymph node status, tumour size, histological grade and oestrogen receptor status) were determined concurrently in these mammary carcinomas. No significant relationship was found between the macrophage content of the mammary carcinomas and any individual prognostic factor. When the patients were grouped according to whether they had 0-2 or 3-4 high risk factors, however, the macrophage content was significantly greater in those tumours with the poorer prognosis, regardless of the marker used to enumerate the cells. A high macrophage content, therefore, is not associated with favourable prognostic factors in breast cancer. Indeed, the present study has revealed the reverse to be the case.


[Preliminary study of the spatial structural and functional changes of dystrophin after exon-3 deletion].
To explore the structural and functional changes of dystrophin molecule after exon 3 deletion. Three-dimensional models of dystrophin comprising the major domains were established before and after exon 3 deletion using SWISS-MODEL server. The motifs and structural domains of dystrophin after exon 3 deletion were searched in Pfam database, and the crystal structure of the actin-binding domain in the dystrophin molecule was analyzed using Rasmol software. Torsion of the N-terminal actin-binding domain occurred in the dystrophin molecule after deletion of exon 3. Homology analysis based on Pfam database searches indicated that following exon 3 deletion, the Bit score of the first calponin homology (CH1) domain was decreased from 108 to 36.5 while its expectation value increased from 2.3e-9 to 8.1e-8. The deletion also resulted in the absence of the spiral region C from the CH1 domain. Exon 3 deletion in the dystrophin-coding sequence decreases the stability of CH1 domain and prevents the formation of the junction interface where dystrophin binds to actin. The bioinformatics approach provides a new alternative for investigation of the pathogenesis of DMD pathogenesy investigation.


The Keto-Switched Photocatalysis of Reconstructed Covalent Organic Frameworks for Efficient Hydrogen Evolution.
The keto-switched photocatalysis of covalent organic frameworks (COFs) for efficient H2 evolution was reported for the first time by engineering, at a molecular level, the local structure and component of the skeletal building blocks. A series of imine-linked BT-COFs were synthesized by the Schiff-base reaction of 1, 3, 5-benzenetrialdehyde with diamines to demonstrate the structural reconstruction of enol to keto configurations by alkaline catalysis. The keto groups of the skeletal building blocks served as active injectors, where hot π-electrons were provided to Pt nanoparticles (NPs) across a polyvinylpyrrolidone (PVP) insulting layer. The characterization results, together with density functional theory calculations, indicated clearly that the formation of keto-injectors not only made the conduction band level more negative, but also led to an inhomogeneous charge distribution in the donor-acceptor molecular building blocks to form a strong intramolecular built-in electric field. As a result, visible-light photocatalysis of TP-COFs-1 with one keto group in the skeletal building blocks was successfully enabled and achieved an impressive H2 evolution rate as high as 0.96 mmol g-1 h-1 . Also, the photocatalytic H2 evolution rates of the reconstructed BT-COFs-2 and -3 with two and three keto-injectors were significantly enhanced by alkaline post-treatment.


[Resources and justice: for an equity on an epidemiological basis of healthcare funding].
The rules for distributing public resources for healthcare among Italian Regions are the subject of heated discussions every year among the Regions themselves. The factors of convenience with respect to those of justice very often prevail in the discussion. To think about what the best solution would be, it would be necessary to deepen the theories of justice, from utilitarianism to contractualism, from liberalism to economic egalitarianism. In any case, it would be advisable for the political choice of the allotment criteria to be made "under the veil of ignorance", i.e., independently of pure convenience. The analysis of the current division shows that the factor that practically explains the totality of the differences is the average age of the regional populations, while it does not seem to be associated with both economic and epidemiological indicators.


InfAcrOnt: calculating cross-ontology term similarities using information flow by a random walk.
Since the establishment of the first biomedical ontology Gene Ontology (GO), the number of biomedical ontology has increased dramatically. Nowadays over 300 ontologies have been built including extensively used Disease Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of identifying novel relationships between terms, calculating similarity between ontology terms is one of the major tasks in this research area. Though similarities between terms within each ontology have been studied with in silico methods, term similarities across different ontologies were not investigated as deeply. The latest method took advantage of gene functional interaction network (GFIN) to explore such inter-ontology similarities of terms. However, it only used gene interactions and failed to make full use of the connectivity among gene nodes of the network. In addition, all existent methods are particularly designed for GO and their performances on the extended ontology community remain unknown. We proposed a method InfAcrOnt to infer similarities between terms across ontologies utilizing the entire GFIN. InfAcrOnt builds a term-gene-gene network which comprised ontology annotations and GFIN, and acquires similarities between terms across ontologies through modeling the information flow within the network by random walk. In our benchmark experiments on sub-ontologies of GO, InfAcrOnt achieves a high average area under the receiver operating characteristic curve (AUC) (0.9322 and 0.9309) and low standard deviations (1.8746e-6 and 3.0977e-6) in both human and yeast benchmark datasets exhibiting superior performance. Meanwhile, comparisons of InfAcrOnt results and prior knowledge on pair-wise DO-HPO terms and pair-wise DO-GO terms show high correlations. The experiment results show that InfAcrOnt significantly improves the performance of inferring similarities between terms across ontologies in benchmark set.


[Etiology of acute and chronic pyelonephritis in children in Khabarovsk region].
Microflora of urinary tract was studied in 419 children aged 1 - 17 years and hospitalized due to acute or chronic pyelonephritis. Etiology of inflammatory process was established in 57.8% of cases. According to our study, etiologic structure of causative agents of pyelonephritis did not differ from all-Russian data. The leading positions belonged to Gram-negative microorganisms from Enterobacteriaceae family: Escherichia coli, Proteus mirabilis, and Klebsiella spp. Results of the study point to high susceptibility of main causative agents of pyelonephritis to cephalosporins, aminoglycosides, and fluoroquinolones. High resistance to aminopenicillines was noted. In several isolates from Enterobacteriaceae family significant resistance to nalidixic acid and furazidin was observed.


Tailoring ultra-fast charge transfer in MoS2.
Charge transfer dynamics are of importance in functional materials used in devices ranging from transistors to photovoltaics. The understanding of charge transfer in particular of how fast electrons tunnel away from an excited state and where they end up, is necessary to tailor materials used in devices. We have investigated charge transfer dynamics in different forms of the layered two-dimensional material molybdenum disulphide (MoS2, in single crystal, nanocrystalline particles and crystallites in a reduced graphene oxide network) using core-hole clock spectroscopy. By recording the electrons in the sulphur KLL Auger electron kinetic energy range we have measured the prevalence of localised and delocalised decays from a state created by core excitation using X-rays. We show that breaking the crystal symmetry of the single crystal into either particles or sheets causes the charge transfer from the excited state to occur faster, even more so when incorporating it in a graphene oxide network. The interface between the MoS2 and the reduced graphene oxide forms a Schottky barrier which changes the ratio between local and delocalised decays creating two distinct regions in the charge transfer dependent on the energy of the excited electron. Thereby we show that ultra-fast charge transfer in MoS2 can be tailored, a result which can be used in the design of emergent devices.


Cardiac conduction velocity estimation from sequential mapping assuming known Gaussian distribution for activation time estimation error.
In this paper, we study the problem of the cardiac conduction velocity (CCV) estimation for the sequential intracardiac mapping. We assume that the intracardiac electrograms of several cardiac sites are sequentially recorded, their activation times (ATs) are extracted, and the corresponding wavefronts are specified. The locations of the mapping catheter's electrodes and the ATs of the wavefronts are used here for the CCV estimation. We assume that the extracted ATs include some estimation errors, which we model with zero-mean white Gaussian noise values with known variances. Assuming stable planar wavefront propagation, we derive the maximum likelihood CCV estimator, when the synchronization times between various recording sites are unknown. We analytically evaluate the performance of the CCV estimator and provide its mean square estimation error. Our simulation results confirm the accuracy of the proposed method and the error analysis of the proposed CCV estimator.


MicroRNA-20a promotes non-small cell lung cancer proliferation by upregulating PD-L1 by targeting PTEN.
Non-small cell lung cancer (NSCLC) remains one of the most common malignant tumors worldwide. The aim of the present study was to investigate the possibility of microRNA-20a (miR-20a) as a biomarker and therapeutic target for the diagnosis and treatment of NSCLC. Bioinformatics prediction, together with functional validation, confirmed miR-20a bound to programmed death ligand-1 (PD-L1) 3'-untranslated region to upregulate PD-L1 expression. Both miR-20a and PD-L1 could promote the proliferation of NSCLC cells. The expression level of PD-L1 was controlled by PTEN; however, further upstream regulation of PD-L1 expression was largely unknown. The present study showed that miR-20a could not restore the inhibition of PD-L1 expression levels by PTEN. Knockdown of PTEN expression upregulated the expression level of PD-L1 and promoted the proliferation of NSCLC cells. PTEN negatively regulated the Wnt/β-catenin signaling pathway by inhibiting β-catenin and Cyclin D1. Interestingly, PTEN could reverse miR-20a-mediated proliferation of NSCLC cells and the inhibitory effect was similar to that of XAV-939. miR-20a promotes the proliferation of NSCLC cells by inhibiting the expression level of PTEN and upregulating the expression level of PD-L1. It is suggested that miR-20a could be used as a biomarker and therapeutic target for the treatment of NSCLC.


Long-acting and short-acting diuretics in mild essential hypertension.
A randomised, placebo-controlled, double-blind crossover study was conducted in 14 patients with mild essential hypertension comparing different regimens of administration of the "short-acting" diuretic, chlorothiazide and the "long-acting" diuretic, chlorthalidone. There were 6 randomised treatment phases each of 5 weeks duration. For blood pressure recorded both at the Clinic and at home the most prominent effects were seen with standing blood pressure, for which significant reductions of mean blood pressure compared to the placebo phase were observed with chlorthalidone 25 mg once daily (-5 +/- 1 (SE) mm Hg - p less than 0.05), chlorthalidone 50 mg once daily (-7 +/- 1 mm Hg - p less than 0.01) and chlorothiazide 500 mg twice daily (-4 +/- 1 mm Hg - p less than 0.05). Blood pressure reductions with chlorothiazide 500 mg once daily and 1000 mg once daily were not significant. About half of the patients completing the trial could be described as "non-responders". The observed biochemical changes (reduced plasma potassium and chloride concentrations and increased plasma bicarbonate and urate concentrations) were most marked in the phases with the most prominent blood pressure effects. The result support the suggestion that a sustained diuretic effect is desirable when diuretics are used in the treatment of hypertension. This can be obtained by selection of the appropriate dosage regimen for a particular diuretic, such as once daily administration for "long-acting" and twice daily for "short-acting" thiazide-type diuretics.


[Influence of climatic factor on formation and development of TCM].
Climatic factors influence health, physiological and pathological condition of human being, and then influence medicine. Through discussing the relationship between climatic type and traditional Chinese medical theory, relationship between climatic changes and formation and development of Cold-Warm School, and regional characteristic of Ling Nan medicine, conclusion can be made: firstly, traditional Chinese medical theory has some regional limit because its formation was influenced by climatic factor; secondly, climatic changes in history is the important cause leading to formation and vicissitude of Cold-Warm School in TCM history; thirdly, as an important branch of TCM, Ling Nan medicine reflects its own climatic characteristic and shows good adaptability and promising prospects of TCM.


Conduction properties of thin films from a water soluble carbon nanotube/hemicellulose complex.
We have examined the conductive properties of carbon nanotube based thin films, which were prepared via dispersion in water by non-covalent functionalization of the nanotubes with xylan, a type of hemicellulose. Measurements of low temperature conductivity, Kelvin probe force microscopy, and high frequency (THz) conductivity elucidated the intra-tube and inter-tube charge transport processes in this material. The measurements show excellent conductive properties of the as prepared thin films, with bulk conductivity up to 2000 S cm-1. The transport results demonstrate that the hemicellulose does not seriously interfere with the inter-tube conductance.


Kinetic analysis of the effect of (-)-epigallocatechin gallate on the DNA scission induced by Fe(II).
The DNA strand scission induced by Fe(II) in a citrate buffer solution and the effect of (-)-epigallocatechin gallate (EGCg) were kinetically analyzed. The rate of consumption of dissolved oxygen by Fe(II) in each of these solutions was measured and paralleled that DNA scission. Coordinated EGCg accelerated these reactions. Curves of the time-course characteristics of DNA scission were simulated by using the rate constant of oxygen consumption and by assuming that scission with the hydroxyl radical (OH), which was formed from the dissolved oxygen, proceeded competitively with the scavenging of OH by citrate, Cl- ions and EGCg added. Free EGCg acted as a DNA scission inhibitor to scavenge OH, in contrast to the case of the coordinated one. This analysis is useful for estimating the rate constant of the reaction between an antioxidant and OH, and might provide a new method for measuring the OH-scavenging activity.


Antipsychotic drug efficacy correlates with the modulation of D1 rather than D2 receptor-expressing striatal projection neurons.
Elevated dopamine transmission in psychosis is assumed to unbalance striatal output through D1- and D2-receptor-expressing spiny-projection neurons (SPNs). Antipsychotic drugs are thought to re-balance this output by blocking D2 receptors (D2Rs). In this study, we found that amphetamine-driven dopamine release unbalanced D1-SPN and D2-SPN Ca2+ activity in mice, but that antipsychotic efficacy was associated with the reversal of abnormal D1-SPN, rather than D2-SPN, dynamics, even for drugs that are D2R selective or lacking any dopamine receptor affinity. By contrast, a clinically ineffective drug normalized D2-SPN dynamics but exacerbated D1-SPN dynamics under hyperdopaminergic conditions. Consistent with antipsychotic effect, selective D1-SPN inhibition attenuated amphetamine-driven changes in locomotion, sensorimotor gating and hallucination-like perception. Notably, antipsychotic efficacy correlated with the selective inhibition of D1-SPNs only under hyperdopaminergic conditions-a dopamine-state-dependence exhibited by D1R partial agonism but not non-antipsychotic D1R antagonists. Our findings provide new insights into antipsychotic drug mechanism and reveal an important role for D1-SPN modulation.


Assembly of an antiparallel homo-adenine DNA duplex by small-molecule binding.
Molecules that reversibly bind DNA and trigger the formation of non-Watson-Crick secondary structures would be useful in the design of dynamic DNA nanostructures and as potential leads for new therapeutic agents. We demonstrate that coralyne, a small crescent-shaped molecule, promotes the formation of a duplex secondary structure from homo-adenine oligonucleotides. AFM studies reveal that the staggered alignment of homo-adenine oligonucleotides upon coralyne binding produces polymers of micrometers in length, but only 2 nm in height. A DNA duplex was also studied that contained eight A.A mismatches between two flanking 7-bp Watson-Crick helices. CD spectra confirm that the multiple A.A mismatches of this duplex bind coralyne in manner similar to that of homo-adenine oligonucleotides. Furthermore, the melting temperature of this hybrid duplex increases by 13 degrees C upon coralyne binding. These observations illustrate that the helical structure of the homo-adenine-coralyne duplex is compatible with the B-form DNA helix.


Impulsiveness in patients with bulimia nervosa: electrophysiological evidence of reduced inhibitory control.
Bulimia nervosa (BN) is associated with a deficit of self-regulatory control and impulsivity. The present study aimed to clarify whether an impaired inhibitory control due to hyperarousal underlies impulsivity in BN subjects. Event-related potentials (ERPs) were recorded in 17 female patients with BN and 17 healthy controls during a three-tone oddball task. ERP components related to inhibition of irrelevant distractor stimuli, as well as effortful processing, were analyzed. Standardized low-resolution electromagnetic tomography (sLORETA) was used to assess ERP source activity. Compared to healthy controls, BN patients showed reduced amplitude and shorter latency of the N200 (N2), increased amplitude and shorter latency of the target slow wave (SW), and higher amplitude of the P300 for distractor stimuli (P3a) and for targets (P3b). sLORETA showed the following: (1) higher activity of the P3a generators in the left parietal cortex, bilateral precuneus and right frontal and anterior cingulate for distractor stimuli and (2) lower activity of the SW generators in the left medial frontal gyrus, bilateral superior frontal, anterior cingulate and cuneus for target stimuli. The reduction of the N2 latency was associated with the Barratt scores for impulsiveness. The observed electrophysiological abnormalities suggest a condition of hyperarousal, with impaired suppression of irrelevant stimuli due to abnormal cortical activation and reduced signal-to-noise ratio. Our findings point to functional abnormalities within a neural system that subserves attention and self-regulatory control, which may contribute to impulsive behaviors in BN.


Boosting peripheral BDNF rescues impaired in vivo axonal transport in CMT2D mice.
Gain-of-function mutations in the housekeeping gene GARS1, which lead to the expression of toxic versions of glycyl-tRNA synthetase (GlyRS), cause the selective motor and sensory pathology characterizing Charcot-Marie-Tooth disease (CMT). Aberrant interactions between GlyRS mutants and different proteins, including neurotrophin receptor tropomyosin receptor kinase receptor B (TrkB), underlie CMT type 2D (CMT2D); however, our pathomechanistic understanding of this untreatable peripheral neuropathy remains incomplete. Through intravital imaging of the sciatic nerve, we show that CMT2D mice displayed early and persistent disturbances in axonal transport of neurotrophin-containing signaling endosomes in vivo. We discovered that brain-derived neurotrophic factor (BDNF)/TrkB impairments correlated with transport disruption and overall CMT2D neuropathology and that inhibition of this pathway at the nerve-muscle interface perturbed endosome transport in wild-type axons. Accordingly, supplementation of muscles with BDNF, but not other neurotrophins, completely restored physiological axonal transport in neuropathic mice. Together, these findings suggest that selectively targeting muscles with BDNF-boosting therapies could represent a viable therapeutic strategy for CMT2D.


Demographic and clinical characteristics of motor vehicle accident victims in the community general health outpatient clinic: a comparison of PTSD and non-PTSD subjects.
Motor vehicle accidents (MVAs) are the leading cause of posttraumatic stress disorder (PTSD) in the general population, often with enduring symptomatology. This study details epidemiological and clinical features that characterize PTSD among MVA victims living in a nonhospitalized community setting long after the MVA event, and includes exploration of premorbid and peritraumatic factors. MVA victims (n=60; 23 males, 37 females) identified from the registry of a community general health outpatient clinic during a 7-year period were administered an extensive structured battery of epidemiological, diagnostic and clinical ratings. Results indicated that 30 subjects (50%; 12 males, 18 females) had MVA-related PTSD (MVAR-PTSD). Among those with PTSD, 16 individuals exhibited PTSD in partial remission, and six, in full remission. There were no significant demographic or occupational function differences between PTSD and non-PTSD groups. The most common comorbid conditions with MVAR-PTSD were social phobia (20%), generalized anxiety disorder (7.8%) and obsessive-compulsive disorder (0.5%). Previous MVA's were not predictive of PTSD. Subjects with MVAR-PTSD scored worse on the Clinician-Administered Posttraumatic Stress Disorder Scale, Part 2 (CAPS-2), Impact of Event Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Impulsivity Scale, and Toronto Alexithymia Rating Scale. Study observations indicate a relatively high rate of PTSD following an MVA in a community-based sample. The relatively high rate of partially remitted MVAR-PTSD (N=16) underscores the importance of subsyndromal forms of illness. Alexithymia may be an adaptive method of coping with event stress. The development of PTSD appears not to be associated with the severity of MVA-related physical injury.


The Clinical Spectrum of Zika Virus in Returning Travelers.
The clinical spectrum of Zika virus had, to date, been described in small series from endemic/epidemic countries and is not well established. We describe the clinical manifestations of laboratory-proven Zika virus infection in Israeli travelers during December 2015-February 2016, and review all published cases of travel-related Zika virus. During the study period, 8 returning Israeli travelers were diagnosed with Zika virus infection. In addition, 41 published cases were included, mostly from Latin America to Europe and North America. Overall, 65.3% were diagnosed by polymerase chain reaction. Rash was the most frequent symptom, present in 95.7% of cases, followed by fever and arthralgia. Conjunctivitis was present in 53.1%; however, only 40.3% presented with a triad of conjunctivitis, fever, and rash. Less frequent symptoms included dysgeusia and nightmares, which, together with arthralgia, persisted for several weeks in some travelers. Zika virus clinical picture in travelers is diverse. Prolonged symptoms may occur.